Objective: The primary objective of this project is to determine if supplementation with multiple vitamin-minerals reduces the incidence of and mortality from esophageal and/or other cancers and reduces total mortality. Secondary objectives are to assess supplement effects on intermediate endpoints in carcinogenesis and to examine new hypotheses relating to the etiology and prevention of upper gastrointestinal cancers. Background: Probably the highest worldwide rates of esophageal cancer occur in Linxian, China, where cumulative death rates to age 75 for this cancer exceed 20%. Widespread deficiencies of multiple nutrients are considered the most likely cause, but consumption of pickled vegetables, moldy foods and nitrosamines and physical trauma from silica fragments in ingested millet may play a role. Methods: Two double-blind, placebo- controlled randomized intervention studies were conducted to evaluate multiple vitamins/minerals in the prevention of esophageal and other cancers. The Dysplasia Trial evaluated 3,318 persons with cytologic evidence of dysplasia supplemented for 6 years, while the General Population Trial evaluated 29,584 persons supplemented for 5 1/4 years. Biologic specimens (blood, toenails, cytology and histology specimens) were collected periodically throughout the trials. Progress: Both trials concluded in 1991, and results showed that the combination of b-carotene/vitamin E/selenium significantly reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Results from endoscopic and cytologic examinations suggested that multiple vitamins/minerals may decrease proliferation and enhance cytologic reversion to nondysplasia. A 5-year post-intervention followup to re-examine trial results is in progress and should be complete in 1997. Nested case-control studies relating baseline serum values of micronutrients, fumonisins, Helicobacter pylori, HPV, and EBV to cancer are in progress.